德國(guó) Nanoanalytics
實(shí)時(shí)無(wú)標(biāo)記細(xì)胞動(dòng)態(tài)分析儀-cellZscope
| 德國(guó) NanoAnalytics公司推出的細(xì)胞跨膜電阻儀（即實(shí)時(shí)無(wú)標(biāo)記細(xì)胞動(dòng)態(tài)分析儀）——cellZscope是由電腦控制，全自動(dòng)、長(zhǎng)時(shí)間實(shí)時(shí)監(jiān)測(cè)細(xì)胞層生理學(xué)參數(shù)的儀器，可實(shí)時(shí)輸出跨膜電阻（TEER）重要指標(biāo)，一次監(jiān)測(cè)樣品6/24/48/72/96個(gè)。尤其適用于細(xì)胞屏障（消化道、呼吸道、血腦屏障）特性，藥物轉(zhuǎn)運(yùn)，納米藥物研發(fā)，中樞神經(jīng)系統(tǒng)疾病，腫瘤等領(lǐng)域的研究。 |
設(shè)備特點(diǎn)
☆ 不干擾細(xì)胞正常生長(zhǎng)環(huán)境---測(cè)量的數(shù)值更加真實(shí)
☆ 超長(zhǎng)時(shí)間全自動(dòng)實(shí)時(shí)分析---測(cè)量的數(shù)據(jù)更加完整
☆ 測(cè)量采用更寬的頻率范圍---擬合的數(shù)據(jù)更加
☆ 構(gòu)建的數(shù)理模型更加細(xì)致---電生理參數(shù)更加豐富
☆ 可兼容多種類(lèi)型培養(yǎng)插件---耗材選擇更加多樣化
技術(shù)原理
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表皮或內(nèi)皮細(xì)胞之間通過(guò)緊密連接形成一層具選擇性的細(xì)胞屏障，細(xì)胞屏障不僅控制鄰近細(xì)胞間間隙對(duì)各種溶解物的擴(kuò)散滲透率，而且調(diào)控跨細(xì)胞物質(zhì)轉(zhuǎn)運(yùn)。細(xì)胞屏障的存在一方面保護(hù)了機(jī)體免受有害物質(zhì)的傷害，另一方面也限制了治療性藥物的進(jìn)入。
細(xì)胞屏障的通透性可以通過(guò)跨膜電阻（即TEER，Transepithelial resistance)來(lái)反映，細(xì)胞屏障的通透性與跨膜電阻TEER之間的關(guān)系為：通透性越高TEER越低，反之亦然。
基本參數(shù)
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☆ 可以直接讀取細(xì)胞屏障層的電阻值TEER (Ω.cm2)；
☆ 完全兼容常用廠家的Transwell細(xì)胞培養(yǎng)皿。包括BD，Biosciences，Corning，Bio-One，Millipore等。無(wú)儀器自帶耗材和其他額外耗材；
☆ 細(xì)胞模塊可以同時(shí)容納6/24/48/72/96個(gè)培養(yǎng)皿。每個(gè)培養(yǎng)皿都有三種型號(hào)可選：小孔型（“24孔”型Transwell培養(yǎng)皿），中孔型（“12孔”型Transwell培養(yǎng)皿），大孔型（“6孔”型Transwell培養(yǎng)皿）；
☆ cellZscope細(xì)胞模塊是放置于標(biāo)準(zhǔn)的細(xì)胞培養(yǎng)箱中，實(shí)時(shí)動(dòng)態(tài)監(jiān)測(cè)，可以監(jiān)測(cè)數(shù)秒到數(shù)周的細(xì)胞動(dòng)態(tài)生物學(xué)行為變化。
應(yīng)用領(lǐng)域
☆ 細(xì)胞屏障（血腦屏障、鼻黏膜及消化道屏障等）的特性
☆ 上皮細(xì)胞、內(nèi)皮細(xì)胞、貼壁細(xì)胞等的跨膜電阻測(cè)量
☆ 緊密連接動(dòng)力學(xué)
☆ 新型藥物研發(fā)
☆ 藥物或毒物對(duì)細(xì)胞屏障功能的影響
☆ 腫瘤侵襲轉(zhuǎn)移
☆ 免疫細(xì)胞在中樞神經(jīng)系統(tǒng)疾病中的作用
設(shè)備型號(hào)
4種不同型號(hào)可供選擇：cellZscopeE、cellZscope+、cellZscope2、cellZscope3
cellZscopeE
☆ 入門(mén)的cellZscopeE型號(hào)更靈活，如果您沒(méi)有較高的通量檢測(cè)，可以選擇cellZscopeE
☆ 多達(dá)6個(gè)通道的TER檢測(cè)
☆ 細(xì)胞培養(yǎng)環(huán)境下實(shí)時(shí)長(zhǎng)時(shí)間檢測(cè)
☆ 可以兼容多種transwell小室
☆ 操作簡(jiǎn)單，清洗方便。
cellZscope+
☆ cellZscope+ 型號(hào)是德國(guó)nanoanalytics公司多年自動(dòng)化細(xì)胞監(jiān)控設(shè)備開(kāi)發(fā)經(jīng)驗(yàn)的成果集中體現(xiàn)
☆ 全面和準(zhǔn)確的阻抗結(jié)果讀取，全頻譜信息
☆ 大的靈活性，不同孔徑的細(xì)胞培養(yǎng)條件可供選擇
☆ 可持續(xù)，易于使用和維護(hù)，不需特殊工具，細(xì)胞模塊上、下部分均可滅菌
☆ cellZscope+型號(hào)設(shè)計(jì)保證了簡(jiǎn)單的操作和大的靈活性。細(xì)胞模塊為研究人員提供了監(jiān)測(cè)所有孔的完整的頂部和基底外側(cè)信息
cellZscope2
☆ cellZscope2新的型號(hào)為基于阻抗的細(xì)胞監(jiān)測(cè)提供了一些全新的體驗(yàn)
☆ 在時(shí)間分辨率達(dá)到了新的高性能基準(zhǔn)。多通道數(shù)據(jù)采集使cellZscope2提供了快、全面的阻抗輸出
☆ 特殊的易用性，更換培養(yǎng)基等細(xì)胞培養(yǎng)常規(guī)操作，無(wú)需插拔數(shù)據(jù)線，數(shù)據(jù)穩(wěn)定性更高
☆ cellZscope2更快的性能允許更高的吞吐量。在實(shí)驗(yàn)前，實(shí)驗(yàn)中和實(shí)驗(yàn)后，方便細(xì)胞模塊與控制模塊的數(shù)據(jù)對(duì)接
cellZscope3
☆ 四個(gè)細(xì)胞模塊，每個(gè)有24個(gè)孔，可以連接到一個(gè)cellZscope3控制器，同時(shí)測(cè)量96個(gè)孔
☆ 自動(dòng)化的，快速的全程監(jiān)控，獲得數(shù)天或數(shù)周的長(zhǎng)期監(jiān)測(cè)數(shù)據(jù)
☆ 特殊的易用性，更換培養(yǎng)基等細(xì)胞培養(yǎng)常規(guī)操作，無(wú)需插拔數(shù)據(jù)線，數(shù)據(jù)穩(wěn)定性更高
☆ 時(shí)間分辨率高：cellZscope3每30秒完成單個(gè)細(xì)胞模塊即24孔的檢測(cè)
四種型號(hào)詳細(xì)比較
cellZscopeE | cellZscope+ | cellZscope2 | cellZscope3 | |
支持transwell小室尺寸 | 6-/12-/24-well | 6-/12-/24-well | 6-/12-/24-well | 6-/12-/24-well |
不同transwell小室尺寸組合 | √ | √ | √ | √ |
與標(biāo)準(zhǔn)transwell小室兼容性 | √ | √ | √ | √ |
細(xì)胞模塊部件可滅菌 | √ | √ | √ | √ |
測(cè)量速度 | 6孔全部完成約1min | 24孔全部完成約4min | 24孔全部完成約1..2min | 每24孔全部完成約30s |
細(xì)胞模塊底座 | 無(wú) | 無(wú) | √ | √ |
可讀取參數(shù) | TER/ Rmed | TER/Ccl/Rmed/Rins/ Cins/CPE_A/CPE_n | TER/Ccl/Rmed/Rins/ Cins/CPE_A/CPE_n | TER/Ccl/Rmed/Rins/ Cins/CPE_A/CPE_n |
細(xì)胞模塊well數(shù) | 6 | 24 | 24 | 96 |
6-well size | √ | √ | √ | √ |
12-well size | √ | √ | √ | √ |
24-well size | √ | √ | √ | √ |
應(yīng)用案例
■ 用跨膜電阻（TEER）值法檢測(cè)Caco-2細(xì)胞屏障的完整性應(yīng)用案例
用跨膜電阻（TEER）值法檢測(cè)Caco-2細(xì)胞屏障的完整性。Caco-2細(xì)胞以5×103細(xì)胞/孔的密度接種于Transwell小室中。周每隔更換一次新鮮培養(yǎng)基，然后在接下來(lái)的兩周每天更換一次新鮮培養(yǎng)基。并使用NanoAnalytics公司 Cellzscope2軟件對(duì)所得實(shí)時(shí)數(shù)據(jù)進(jìn)行分析。
Caco-2細(xì)胞培養(yǎng)19天后，細(xì)胞跨膜電阻值≥500 Ω·cm2，細(xì)胞形成一個(gè)完整的單層屏障，完整性通過(guò)Lucifer Yellow滲透性測(cè)試得到進(jìn)一步得到證實(shí)，進(jìn)而單層細(xì)胞屏障可用于下一步的運(yùn)輸實(shí)驗(yàn)。SRL和SRL NCs的細(xì)胞毒性呈濃度依賴(lài)性（圖1B）。SRL和SRL-NCs的半數(shù)大抑菌濃度分別為147.51μg/mL和165.41μg/mL。在50μg/mL的SRL和SRL-NCs作用72h后，細(xì)胞存活率保持在80%以上。這表明本研究中使用的SRL濃度不會(huì)引起顯著的細(xì)胞毒性。因此，藥物對(duì)細(xì)胞活力的影響可以忽略不計(jì)。
轉(zhuǎn)運(yùn)實(shí)驗(yàn)采用完整緊密連接的腸上皮Caco-2細(xì)胞單層作為模型，SRL和SRL-NCs組的跨膜電阻（TEER）值（圖1D）在整個(gè)轉(zhuǎn)運(yùn)過(guò)程中未顯示出任何顯著變化，表明在沒(méi)有緊密連接遭到破壞的情況下，Caco-2細(xì)胞單層的完整性得以維持。
將含藥物HBSS緩沖液和空白HBSS緩沖液分別添加到模型頂層（AP）和基底外側(cè)（BL）側(cè)，模擬藥物從GIT到血液的吸收和轉(zhuǎn)運(yùn)途徑。也就是說(shuō)，細(xì)胞層從GIT中運(yùn)出藥物并將其輸送到血液/腸系膜淋巴。相反，當(dāng)將藥物HBSS緩沖液添加到BL側(cè)和空白HBSS緩沖液添加到AP側(cè)時(shí)，模擬了動(dòng)物血液進(jìn)入腸腔的過(guò)程。計(jì)算出SRL-NCs的流出速率由于Papp、BL-AP/Papp、AP-BL與SRL顯著不同（圖1C）。原因可能是藥物被納米化后藥物變得更小，比表面積增加，因此跨單層的轉(zhuǎn)運(yùn)顯著增強(qiáng)。另一種可能是細(xì)胞占據(jù)了整個(gè)SRL-NCs結(jié)構(gòu)，因此與SRL組相比，通透性增強(qiáng)，SRL-NCs組AP→BL側(cè)Papp高5.6倍，外排率低。
圖1 SRL和SRL-NCs在Caco-2細(xì)胞單層屏障的轉(zhuǎn)運(yùn)。（A）跨膜轉(zhuǎn)運(yùn)實(shí)驗(yàn)示意圖；（B）不同濃度SRL和SRL-NCs對(duì)Caco-2細(xì)胞活力的影響（n=6）。（C）SRL和SRL-NCs-Papp、A-B、Papp、B-A和Caco-2細(xì)胞單層的流出比（n=*6，*P<0.01）。（D）Caco-2細(xì)胞單層TEER值在整個(gè)轉(zhuǎn)運(yùn)過(guò)程中的變化。數(shù)據(jù)表示為平均標(biāo)準(zhǔn)差。
數(shù)據(jù)測(cè)試
1.細(xì)胞屏障的特性
cellZscope可以連續(xù)監(jiān)測(cè)細(xì)胞幾天甚至幾星期的生理狀態(tài)。從cellZscope所提供的跨膜電阻值（TEER）和電容值（Ccl）這兩個(gè)參數(shù)可以獲知當(dāng)前的細(xì)胞狀態(tài)，包括融合度和分化度。CaCO2是源自人類(lèi)結(jié)腸癌細(xì)胞系，通常用于藥物轉(zhuǎn)運(yùn)研究，圖中cellZscope跟蹤記錄了CaCO2細(xì)胞層的形成和分化的信息，自動(dòng)化的記錄了從接種細(xì)胞開(kāi)始并持續(xù)觀察21天。
長(zhǎng)時(shí)間監(jiān)測(cè)細(xì)胞屏障的形成
2.緊密連接動(dòng)力學(xué)
上皮細(xì)胞和內(nèi)皮細(xì)胞的跨膜阻抗值與細(xì)胞間緊密連接密切相關(guān)。緊密連接可影響細(xì)胞間物質(zhì)轉(zhuǎn)運(yùn)過(guò)程。通過(guò)cellZscope測(cè)量細(xì)胞層跨膜電阻可以用于研究緊密連接動(dòng)力學(xué)。圖示MDCK細(xì)胞對(duì)不同濃度的EGTA的反應(yīng)。
細(xì)胞緊密動(dòng)力學(xué)研究
3.新型藥物研發(fā)
4.藥物或毒物對(duì)細(xì)胞屏障功能的影響
5.腫瘤侵襲轉(zhuǎn)移
6.免疫細(xì)胞在中樞神經(jīng)系統(tǒng)疾病中的作用
發(fā)表文章
2021
1. Comparative sensitivity of proliferative and differentiated intestinal epithelial cells to the food contaminant, deoxynivalenol
S. Luo, Ch. Terciolo, M. Neves, S. Puel, Cl. Naylies, Y. Lippi, Ph. Pinton, I.P. Oswald. Environ. Pollut. 277, 116818 (2021).
→ doi: 10.1016/j.envpol.2021.116818
2. Human induced pluripotent stem cells (BIONi010-C) generate tight cell monolayers with blood-brain barrier traits and functional expression of large neutral amino acid transporter 1 (SLC7A5)
C. Goldeman, M. Andersen, A. Al-Robai, T. Buchholtz, N. Svane, B. Ozgür, B. Holst, E. Shusta, V. Hall, L. Saaby, P. Hyttel, B. Brodin, Eur. J. Pharm. Sci. 156, 105577 (2021).
→ doi: 10.1016/j.ejps.2020.105577
3. The effect of ultrasound cavitation on endothelial cells
M.S. Karthikesh, X. Yang. Exp. Biol. Med. XX, YY (2021).
→ doi: 10.1177/1535370220982301
4. Towards the development of a human in vitro model of the blood–brain barrier for virus-associated acute encephalopathy: assessment of the time- and concentration-dependent effects of TNF-a on paracellular tightness
H. Maeda, K. Hashimoto, H. Go, K. Miyazaki, M. Sato, Y. Kawasaki, N. Momoi, M. Hosoya. Exp. Brain Res. 239, 451 (2021).
→ doi: 10.1007/s00221-020-05985-7
5. Generation and Characterization of Immortalized Mouse Cortical Astrocytes From Wildtype and Connexin43 Knockout Mice
A. Cibelli, S.V. Lopez-Quintero, S. McCutcheon, E. Scemes, D.C. Spray, R.F. Stout Jr., S.O. Suadicani, M.M. Thi, M. Urban-Maldonado Front. Cell. Neurosci. 15, 647109 (2021).
→ doi: 10.3389/fncel.2021.647109
6. Lecithin coating as universal stabilization and functionalization strategy for nanosized drug carriers to overcome the blood–brain barrier
A.Wünsch, D.Mulac, K.Langer. Int. J. Pharm. 593, 120146 (2021).
→ doi: 10.1016/j.ijpharm.2020.120146
7. AMP-activated protein kinase is a key regulator of acute neurovascular permeability
S. Dragoni, B. Caridi, E. Karatsai, T. Burgoyne, M.H. Sarker, P. Turowski. J. Cell Sci. XX, YY (2021).
8. Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins
L. Winkler, R. Blasig, O. Breitkreuz-Korff, Ph. Berndt, S. Dithmer, H.C. Helms, D. Puchkov, K. Devraj, M. Kaya, Z. Qin, S. Liebner, H. Wolburg, A.V. Andjelkovic, A. Rex, I.E. Blasig, R.F. Haseloff, J. Cereb. Blood Flow Metab. 41, 132 (2021).
→ doi: 10.1177/0271678X20904687
9. Meprin ?: A novel regulator of blood–brain barrier integrity
M. Gindorf, S.E. Storck, A. Ohler, F. Scharfenberg, Ch. Becker-Pauly, C.U. Pietrzik, J. Cereb. Blood Flow Metab. 41, 31 (2021).
→ doi: 10.1177/0271678X20905206
10. Macrophage-mediated vascular permeability via VLA4/VCAM1 pathway dictates ascites development in ovarian cancer
S. Zhang, B. Xie, L. Wang, H. Yang, H. Zhang, Y. Chen, F. Wang, Ch. Liu, H. He, J. Clin. Invest. 131, e140315 (2021).
11. Development of an In Vitro Airway Epithelial–Endothelial Cell Culture Model on a Flexible Porous Poly(Trimethylene Carbonate) Membrane Based on Calu-3 Airway Epithelial Cells and Lung Microvascular Endothelial Cells
T. Pasman, D. Baptista, S. van Riet, R.K. Truckenmüller, P.S. Hiemstra, R.J. Rottier, N.M. Hamelmann, J.M.J. Paulusse, D. Stamatialis, á.A. Poot Membranes 11, 197 (2021).
→ doi: 10.3390/membranes11030197
12. Capabilities of selenoneine to cross the in vitro blood–brain barrier model
E. Drobyshev, S. Raschke, R.A. Glabonjat, J. Bornhorst, F. Ebert, D. Kuehnelt, T. Schwerdtle. Metallomics 13, mfaa007 (2021).
13. TGF-?1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei
C. Schilpp, R. Lochbaum, P. Braubach, D. Jonigk, M. Frick, P. Dietl, O.H. Wittekindt. Pfluegers Arch. 473, 287 (2021).
→ doi: 10.1007/s00424-020-02501-2
14. SZR-104, a Novel Kynurenic Acid Analogue with High Permeability through the Blood–Brain Barrier
K. Molnár, B. Lorinczi, C. Fazakas, I. Szatmári, F. Fül?p, N. Kmetykó, R. Berkecz, I. Ilisz, I.A. Krizbai, I. Wilhelm,L. Vécsei. Pharmaceutics 13, 61 (2021).
→ doi: 10.3390/pharmaceutics13010061
15. Endothelial Iron Homeostasis Regulates Blood-Brain Barrier Integrity via the HIF2a—Ve-Cadherin Pathway
D. Rand, O. Ravid, D. Atrakchi, H. Israelov, Y. Bresler, Ch. Shemesh, L. Omesi, S. Liraz-Zaltsman, F. Gosselet, T.S. Maskrey, M. Schnaider Beeri, P. Wipf, I. Cooper Pharmaceutics 13, 311 (2021).
→ doi: 10.3390/pharmaceutics13030311
16. Astrocyte-derived Wnt growth factors are required for endothelial blood-brain barrier maintenance
S. Guerit, E. Fidan, J. Macas, C.J. CCzupalla, R. Figueiredo, A. Vijikumar, B.H. Yalcin, S. Thom, P. Winter, H. Gerhardt, K. Devraj, S. Liebner. Prog. Neurobiol. 199, 101937 (2021).
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17. Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock
S. Chakraborty, V.E. Winkelmann, S. Braumüller, A. Palmer, A. Schultze, B. Klohs, A. Ignatius, A. Vater, M. Fauler, M. Frick, M. Huber-Lang. Sci. Rep. 11, 2158 (2021).
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18. Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo
K. Ernst, A.-K. Mittler, V. Winkelmann, C. Kling, N. Eberhardt, A. Anastasia, M. Sonnabend, R. Lochbaum, J. Wirsching, M. Sakari, A.T. Pulliainen, C. Skerry, N.H. Carbonetti, M. Frick, H. Barth. Sci. Rep. 11, 5429 (2021).
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19. Repeated exposure of Caco-2 versus Caco-2/HT29-MTX intestinal cell models to (nano)silver in vitro: Comparison of two commercially available colloidal silver products
20. K. Gillois, Ch. Stoffels, M. Leveque, I. Fourquaux, J. Blesson, V. Mils, S. Cambier, J. Vignard, H. Terrisse, G. Mirey, J.-N. Audinot, V. Theodorou, M.-H. Ropers, H. Robert, M. Mercier-Bonin. Sci. Total Environ. 754, 14232 (2021).
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21. Microfluidic In Vitro Platform for (Nano)Safety and (Nano)Drug Efficiency Screening
Y. Kohl, M. Biehl, S. Spring, M. Hesler, V. Ogourtsov, M. Todorovic, J. Owen, E. Elje, K. Kopecka, O.H. Moriones, N.G. Bastús, P. Simon, T. Dubaj, E. Rundén-Pran, V. Puntes, N. William, H. von Briesen, S. Wagner, N. Kapur, E. Mariussen, A. Nelson, A. Gabelova, M. Dusinska, Th. Velten, Th. Knoll. Small XX, YY (2021).
22. Human Astroviruses: A Tale of Two Strains
V. Hargest, A.E. Davis, S. Tan, V. Cortez, S. Schultz-Cherry. Viruses 13, 376 (2021).
2020
Genomic and phenotypic stability of Lactobacillus rhamnosus GG in an industrial production process
M. Stage, A. Wichmann Gustafsson, M. J?rgensen, N.I. Vera-Jimenéz, M. Wielje, D.S. Nielsen, A. Sandelin, Y. Chen, A. Baker
Appl. Environ. Microbiol. XX, YY (2020).
Retinoic acid signalling adjusts tight junction permeability in response to air-liquid interface conditions
R. Lochbaum, C. Schilpp, L. Nonnenmacher, M. Frick, P. Dietl, O.H. Wittekindt
Cell. Signalling 65, 1094213 (2020).
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Synthesis and in vitro evaluation of cyclodextrin hyaluronic acid conjugates as a new candidate for intestinal drug carrier for steroid hormones
M. Heslera, D.H.Schwarz, S. D?hnhardt-Pfeiffer, S. Wagner, H. von Briesen, G. Wenz, Y. Kohl
Eur. J. Pharm. Sci. 143, 105181 (2020).
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Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS
S. Edogawa, A. Ledwinson, S.A. Peters, L.L. Chikkamenahalli, W. Sundt, S. Graves, S.V. Gurunathan, M. Breen-Lyles, S. Johnson, R. Dyer, R. Graham, J. Chen, P. Kashyap, G. Farrugia, M. Grover
Gut 69, 62 (2020).
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TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function
G. Merlen, N. Kahale, J. Ursic-Bedoya, V. Bidault-Jourdainne, H. Simerabet, I. Doignon, Z. Tanfin, I. Garcin, N. Péan, J. Gautherot, A. Davit-Spraul, C. Guettier, L. Humbert, D. Rainteau, K. Ebnet, Ch. Ullmer, D. Cassio, T. Tordjmann
Gut 69, 146 (2020).→ doi: 10.1136/gutjnl-2018-31697
Enteropathogenic Escherichia coli (EPEC) Recruitment of PAR Polarity Protein Atypical PKC? to Pedestals and Cell–Cell Contacts Precedes Disruption of Tight Junctions in Intestinal Epithelial Cells
R. Tapia, S.E. Kralicek, G.A. Hecht
Int. J. Mol. Sci. 21, 527 (2020).
Meprin ?: A novel regulator of blood–brain barrier integrity
M. Gindorf, S.E. Storck, A. Ohler, F. Scharfenberg, Ch. Becker-Pauly, C.U. Pietrzik
J. Cereb. Blood Flow Metab. XX, YY (2020).
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Tight junctions in the blood–brain barrier promote edema formation and infarct size in stroke – Ambivalent effects of sealing proteins
L. Winkler, R. Blasig, O. Breitkreuz-Korff, Ph. Berndt, S. Dithmer, H.C. Helms, D. Puchkov, K. Devraj, M. Kaya, Z. Qin, S. Liebner, H. Wolburg, A.V. Andjelkovic, A. Rex, I.E. Blasig, R.F. Haseloff
J. Cereb. Blood Flow Metab. XX, YY (2020).
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Identification of Parthenolide Dimers as Activators of Pyruvate Kinase M2 in Xenografts of Glioblastoma Multiforme in Vivo
Y. Ding, Q. Xue, S. Liu, K. Hu, D. Wang, T. Wang, Y. Li, H. Guo, X. Hao, W. Ge, Y. Zhang, A. Li J. Li, Y. Chen, Q. Zhang
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Monophosphoryl Lipid a Attenuates Multiorgan Dysfunction During Post-Burn Pseudomonas Aeruginosa Pneumonia in Sheep
S. Fukuda, K. Ihara, J.K. Bohannon, A. Hernandez, N.K. Patil, L. Luan, C. Stothers, R. Stark, D.S. Prough, D.N. Herndon, E.R. Sherwood, P. Enkhbaatar
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Claudin-12 deficiency causes nerve barrier breakdown, mechanical hypersensitivity and painfulness in polyneuropathy
J.T.-C. Chen, X. Hu, K. Doppler, O. Breitkreuz-Korff, I.U.C. Otto, J. Schwabe, A.-K. Reinhold, D. Günzel, S. Dithmer, M.K. Hankir, P. Fallier-Becker, L. Winkler, R. Blasig, C. Sommer, A. Brack, I.E. Blasig, H.L. Rittner
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2019
Enhanced Bioavailability by Orally Administered Sirolimus Nanocrystals
J. Kong, K. Wu, Y. Ji, K. Chen, J. Zhang, H. Sun, Y. Liang, W. Liang, Y. Chang, J. Cheng, J. Tong, J. Li, G. Xing, G. Chen
ACS Appl. Bio Mater. 2, 4612 (2019).
Effect of E Cigarette Emissions on Tracheal Cells Monitored at the Air–Liquid Interface Using an Organic Electrochemical Transistor
M.P. Ferro, L. Leclerc, M. Sleiman, B. Marchiori, J. Pourchez, R.M. Owens, M. Ramuz
Adv. Biosys. 3, 1800249 (2019).
Oxidative Stress Increases Endogenous Complement-Dependent Inflammatory and Angiogenic Responses in Retinal Pigment Epithelial Cells Independently of Exogenous Complement Sources
T.-O. Trakkides, N. Sch?fer, M. Reichenthaler, K. Kühn, R.J.M.G.E. Brandwijk, E.J.M. Toonen, F. Urban, J. Wegener, V. Enzmann, D. Pauly
Antioxidants 8, 548 (2019).
Non-pooled Human Platelet Lysate: A Potential Serum Alternative for In Vitro Cell Culture
M. Hesler, Y. Kohl, S. Wagner, H. von Briesen
ATLA, Altern. Lab. Anim. 47, 116 (2019).
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Differential modulation of transendothelial electrical resistance by TRPV4 agonists is mediated by apoptosis and/or necrosis
N. Pairet , S. Mang, T. Kiechle, N. Laufh?ger, P. Dietl, D.J. Lamb
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Targeting claudin-4 enhances chemosensitivity of pancreatic ductal carcinomas
T. Sasaki, R. Fujiwara-Tani, S. Kishi, S. Mori, Y. Luo, H. Ohmori, I. Kawahara, K. Goto, Y. Nishiguchi, T. Mori, M. Sho, M. Kondo, H. Kuniyasu
Cancer Med. 8, 6700 (2019).
Toll-like receptor 3-mediated inflammation by p38 is enhanced by endothelial nitric oxide synthase knockdown
S.R. Koch, H. Choi, E.H. Mace, R.J. Stark
Cell Commun. Signaling 17, 33 (2019).
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Stimulation of the A2B Adenosine Receptor Subtype Enhances Connexin26 Hemichannel Activity in Small Airway Epithelial Cells
A. Dierksa, A. Badera, T. Lehricha, A. Ngezahayo
Cell. Physiol. Biochem. 53, 606 (2019).
Endothelial tight junctions and their regulatory signaling pathway
X. Cong, W. Kong
Cell. Signalling 66, 109485 (2019).
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Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability
J. Miranda, D. Martín-Tapia, Y. Valdespino-Vázquez, L. Alarcón, A. Espejel-Nu?ez, M. Guzmán-Huerta, J.E. Mu?oz-Medina, M. Shibayama, B. Chávez-Munguía, G. Estrada-Gutiérrez, S. Lievano, J.E. Ludert, L. González-Mariscal
Cells 8, 1174 (2019).
Transient blood–brain barrier disruption isinduced by low pulsed electrical fields in vitro: ananalysis of permeability and trans-endothelialelectric resistivity
S. Sharabi, Y. Bresler, O. Ravid, Ch. Shemesh, D. Atrakchi, M. Schnaider-Beeri, F. Gosselet, L. Dehouck, D. Last, D. Guez, D. Daniels, Y. Mardor, I. Cooper
Drug Delivery 26, 459 (2019).
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In vitro and in vivo effects of a mycotoxin, deoxynivalenol, and a trace metal, cadmium, alone or in a mixture on the intestinal barrier
S. Luo, Ch. Terciolo, A.P.F.L. Bracarense, D. Payros, Ph. Pinton, I.P. Oswald
Environ. Int. 132, 105082 (2019).
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A unified in vitro test system for the assessment of tight junction modulators
D. Saaber, S. Reichl
Eur. J. Pharm. Biopharm. 142, 353 (2019).
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The impact of gastrointestinal mucus on nanoparticle penetration – in vitro evaluation of mucus-penetrating nanoparticles for photodynamic therapy
L. Mahlert, J. Anderski, D. Mulac, K. Langer
Eur. J. Pharm. Sci. 133, 28 (2019).
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Revisiting an old antibiotic: bacitracin neutralizes binary bacterial toxins and protects cells from intoxication
L. Schnell, I. Felix, B. Müller, M. Sadi, F. von Bank, P. Papatheodorou, M.R. Popoff, K. Aktories, E. Waltenberger, R. Benz, C. Weichbrodt, M. Fauler, M. Frick, H. Barth
FASEB J. 33, 5755 (2019).
Impedance Spectroscopy as a Tool for Monitoring Performance in 3D Models of Epithelial Tissues
T. Gerasimenko, S. Nikulin, G. Zakharova, A. Poloznikov, V. Petrov, A. Baranova, A. Tonevitsky
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PECAM-1 Stabilizes Blood-Brain Barrier Integrity and Favors Paracellular T-Cell Diapedesis Across the Blood-Brain Barrier During Neuroinflammation
I. Wimmer, S. Tietz, H. Nishihara, U. Deutsch, F. Sallusto, F. Gosselet, R. Lyck, W.A. Muller, H. Lassmann, B. Engelhardt
Front. Immunol. 10, 711 (2019).
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Autophagy Protects the Blood-Brain Barrier Through Regulating the Dynamic of Claudin-5 in Short-Term Starvation
Z. Yang, Ch. Huang, Y. Wu, B. Chen, W. Zhang, J. Zhang
Front. Physiol. 10, 2 (2019).
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Structure and biological activities of a hexosamine-rich cell wall polysaccharide isolated from the probiotic Lactobacillus farciminis
E. Maes, I. Sadovskaya, M. Lévêque, E. Elass-Rochard, B. Payré, Th. Grard, V. Théodorou, Y. Guérardel, M. Mercier-Bonin
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IL-13 Impairs Tight Junctions in Airway Epithelia
H. Schmidt, P. Braubach, C. Schilpp, R. Lochbaum, K. Neuland, K. Thompson, D. Jonigk, M. Frick, P. Dietl, O.H. Wittekindt
Int. J. Mol. Sci. 20, 3222 (2019).
Temporal Effects of Quercetin on Tight Junction Barrier Properties and Claudin Expression and Localization in MDCK II Cells
E. Gamero-Estevez, S. Andonian, B. Jean-Claude, I. Gupta, A.K. Ryan
Int. J. Mol. Sci. 20, 4889 (2019).
The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers
M. Kaiser, M. Burek, S. Britz, F. Lankamp, S. Ketelhut, B. Kemper, C. F?rster, Ch. Gorzelanny, F.M. Goycoolea
Int. J. Mol. Sci. 20, 122 (2019).
Controversial roles for dexamethasone in glioblastoma – Opportunities for novel vascular targeting therapies
D. Dubinski, E. Hattingen, Ch. Senft, V. Seifert, K.G. Peters, Y. Reiss, K. Devraj, K.H. Plate
J. Cereb. Blood Flow Metab. 39, 1460 (2019).
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Short communication: Processed bovine colostrum milk protein concentrate increases epithelial barrier integrity of Caco-2 cell layers
R.C. Anderson, J.E. Dalziel, N.W. Haggarty, K.E. Dunstan, P.K. Gopal, N.C. Roy
J. Dairy Sci. 102, 10772 (2019).
Impact of Docetaxel on blood-brain barrier function and formation of breast cancer brain metastases
S. Bernatz, E.I. Ilina, K. Devraj, P.N. Harter, K. Mueller, S. Kleber, Y. Braun, C. Penski, Ch. Renner, R. Halder, L. Jennewein, Ch. Solbach, F. Thorsen, B.C. Pestalozzi, A. Mischo, M. Mittelbronn
J. Exp. Clin. Cancer Res. 38, 434 (2019).
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Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood–brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis
S.A. Jassam, Z. Maherally, K. Ashkan, G.J. Pilkington, H.L. Fillmore
J. Neuro-Oncol. 143, 405 (2019).
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Haem iron reshapes colonic luminal environment: impact on mucosal homeostasis and microbiome through aldehyde formation
O.C.B. Martin, M. Olier, S. Ellero-Simatos, N. Naud, J. Dupuy, L. Huc, S. Taché, V. Graillot, M. Levêque, V. Bézirard, C. Héliès-Toussaint, F.B.Y. Estrada, V. Tondereau, Y. Lippi, C. Naylies, L. Peyriga, C. Canlet, A.M. Davila, F. Blachier, L. Ferrier, E. Boutet-Robinet, F. Guéraud, V. Théodorou, F.H.F. Pierre
Microbiome 7, 72 (2019).
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Improved Drug Delivery to Brain Metastases by Peptide-Mediated Permeabilization of the Blood–Brain Barrier
S.N. Aasen, H. Espedal, Ch.F. Holte, O. Keunen, T.V. Karlsen, O. Tenstad, Z. Maherally, H. Miletic, T. Hoang, A.V. Eikeland, H. Baghirov, D.E. Olberg, G.J. Pilkington, G. Sarkar, R.B. Jenkins, T. Sundstr?m, R. Bjerkvig, F. Thorsen
Mol. Cancer Ther. 18, 2171 (2019).
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LRP1 Has a Predominant Role in Production over Clearance of A? in a Mouse Model of Alzheimer’s Disease
B. Van Gool, S.E. Storck, S.M. Reekmans, B. Lechat, Ph.L.S.M. Gordts, L. Pradier, C.U. Pietrzik, A.J.M. Roebroek
Mol. Neurobiol. 56, 7234 (2019).
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Side-directed Transfer and Presystemic Metabolism of Selenoneine in a Human Intestinal Barrier Model
I. Rohn, N. Kroepfl, J. Bornhorst, D. Kuehnelt, T. Schwerdtle
Mol. Nutr. Food Res. 63, 1900080 (2019).
Polyphenol Extracts from Three Colombian Passifloras (Passion Fruits) Prevent Inflammation-Induced Barrier Dysfunction of Caco-2 Cells
J.C. Carmona-Hernandez, G. Taborda-Ocampo, J.C. Valdez, B.W. Bolling, C.H. González-Correa
Molecules 24, 4614 (2019).
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Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology
J.K. Sonner, M. Keil, M. Falk-Paulsen, N. Mishra, A. Rehman, M. Kramer, K. Deumelandt, J. R?we, K. Sanghvi, L. Wolf, A. von Landenberg, H. Wolff, R. Bharti, I. Oezen, T.V. Lanz, F. Wanke, Y. Tang, I. Brandao, S.R. Mohapatra, L. Epping, A. Grill, R. R?th, B. Niesler, S.G. Meuth, Ch.A. Opitz, J.G. Okun Ch. Reinhardt, F.C. Kurschus, W. Wick, H.B. Bode, Ph. Rosenstiel, M. Platten
Nat. Commun. 10, 4877 (2019).
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Crossing the blood-brain-barrier with nanoligand drug carriers self-assembled from a phage display peptide
L.-P. Wu, D. Ahmadvand, J. Su, A. Hall, X. Tan, Z.S. Farhangrazi, S.M. Moghimi
Nat. Commun. 10, 4635 (2019).
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Targeting claudin-4 enhances CDDP-chemosensitivity in gastric cancer
Y. Nishiguchi, R. Fujiwara-Tani, T. Sasaki, Y. Luo, H. Ohmori, S. Kishi, S. Mori, K. Goto, W. Yasui, M. Sho, H. Kuniyasu
Oncotarget 10, 2189 (2019).
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Corticosteroid signaling at the brain-immune interface impedes coping with severe psychological stress
A. Kertser, K. Baruch, A. Deczkowska, A. Weiner, T. Croese, M. Kenigsbuch, I. Cooper, M. Tsoory, S. Ben-Hamo, I. Amit, M. Schwartz
Sci. Adv. 5, eaav4111 (2019).
Claudin-3-deficient C57BL/6J mice display intact brain barriers
M.C. Dias, C. Coisne, I. Lazarevic, P. Baden, M. Hata, N. Iwamoto, D.M.F. Francisco, M. Vanlandewijck, L. He, F.A. Baier, D. Stroka, R. Bruggmann, R. Lyck, G. Enzmann, U. Deutsch, Ch. Betsholtz, M. Furuse, S. Tsukita & B. Engelhardt
Sci. Rep. 9, 203 (2019).
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Unraveling In Vivo Brain Transport of Protein-Coated Fluorescent Nanodiamonds
P. Moscariello, M. Raabe, W. Liu, S. Bernhardt, H. Qi, U. Kaiser, Y. Wu, T. Weil, H.J. Luhmann, J. Hedrich
Small 15, 1902992 (2019).
The Antibiotic Bacitracin Protects Human Intestinal Epithelial Cells and Stem Cell-Derived Intestinal Organoids from Clostridium difficile Toxin TcdB
Z. Zhu, L. Schnell, B. Müller, M. Müller, P. Papatheodorou, H. Barth
Stem Cells Int. 2019, 4149762 (2019).→ doi: 10.1155/2019/4149762
Multi-endpoint toxicological assessment of polystyrene nano- and microparticles in different biological models in vitro
M. Heslera, L. Aengenheister, B. Ellinger, R. Drexel, S. Straskraba, C. Jost, S. Wagner, F. Meier, H. von Briesen, C. Büchel, P. Wick, T. Buerki-Thurnherr, Y. Kohl
Toxicol. In Vitro 61, 104610 (2019).
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Modelling Macular Edema: The Effect of IL-6 and IL-6R Blockade on Human Blood–Retinal Barrier Integrity In Vitro
M. Mesquida, F. Drawnel, P.J. Lait, D.A. Copland, M.L. Stimpson, V. Lloren, M.S. de la Maza, A. Adan, G. Widmer, P. Strassburger, S. Fauser, A.D. Dick, R.W. J. Lee, B. Molins
Transl. Vis. Sci. Techn. 8, 32 (2019).
2018
Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates. Adv. Sci. (2018).
Importance of the IL-1 Axis in Haemophilus influenzae–stimulated M1 Macrophages Driving Transepithelial Signaling. Am. J. Respir. Cell Mol. Biol. (2018).
Effects of arsenolipids on in vitro blood-brain barrier model. Arch. Toxicol. (2018).
Reversible opening of the blood-brain barrier by claudin-5-binding variants of Clostridium perfringens enterotoxin's claudin-binding domain. Biomaterials. (2018).
HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model. EBioMedicine. (2018).
Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood–brain barrier model exemplifies tight-junction integrity. FASEB J. (2018)
Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption. J. Neurochem. (2018).
A novel human induced pluripotent stem cell blood-brain barrier model: Applicability to study antibody-triggered receptor-mediated transcytosis. Sci. Rep. (2018).
Optimized procedures for generating an enhanced, near physiological 2D culture system from porcine intestinal organoids. Stem Cell Res. (2018).
Localized delivery of curcumin into brain with polysorbate 80-modified cerasomes by ultrasound-targeted microbubble destruction for improved Parkinson's disease therapy. Theranostics. (2018).
2017
Insights from mathematical modelling for T cell migration into the central nervous system. Math. Med. Biol. (2017)
Establishment of a method for evaluating endothelial cell injury by TNF-α in vitro for clarifying the pathophysiology of virus-associated acute encephalopathy. Pediatr. Res. (2017)
Development of Blood-Brain Barrier Permeable Nanoparticles as Potential Carriers for Salvianolic Acid B to CNS. Planta Med. (2017)
Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells. Stem Cell Rep. (2017)
Exfoliated graphene nanosheets: pH-sensitive drug carrier and anti-cancer activity. J. Colloid Interface Sci. (2017)
Endothelial Basement Membrane Laminin 511 Contributes to Endothelial Junctional Tightness and Thereby Inhibits Leukocyte Transmigration. Cell Rep. (2017)
Dual role of ALCAM in neuroinflammation and blood–brain barrier homeostasis. PNAS .(2017)
Gb3-binding lectins as potential carriers for transcellular drug delivery. Drug Delivery. (2017)
Early-lactation, but not mid-lactation, bovine lactoferrin preparation increases epithelial barrier integrity of Caco-2 cell layers. J. Dairy Sci. (2017)
Primary porcine brain endothelial cells as in vitro model to study effects of ultrasound on blood-brain barrier function. IEEE Trans. Sonics Ultrason. (2017)
用戶(hù)單位
部分國(guó)內(nèi)用戶(hù)：
| 廣東醫(yī)學(xué)院（湛江） | 天壇醫(yī)院 |
| 中國(guó)食品發(fā)酵研究院 | 醫(yī)科院藥植所 |
| 中科院高能物理研究所 | 上海市疾控中心 |
| 都師范大學(xué) | 上海市第十人民醫(yī)院 |
| 都醫(yī)科大學(xué)-1 | 廣州市血液中心 |
| 深圳先進(jìn)技術(shù)研究院 | 陸軍軍醫(yī)大學(xué) |
| 都醫(yī)科大學(xué)-2 | 浙江省醫(yī)藥學(xué)院 |
| 都醫(yī)科大學(xué)-3 | 山東省農(nóng)科院 |
| GSK上海研發(fā)部 | 成都市第三人民醫(yī)院 |
| 都醫(yī)科大學(xué)-4 | 空軍軍醫(yī)大學(xué)附屬口腔醫(yī)院 |
| 南開(kāi)大學(xué) |
